miR-34a inhibits the migration and invasion of esophageal squamous cell carcinoma by targeting Yin Yang-1
miR-34a inhibits the migration and invasion of esophageal squamous cell carcinoma by targeting Yin Yang-1
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miR-34a通过靶向Yin Yang-1抑制食管鳞癌的迁移和侵袭
DOI：
10.3892/or.2015.3962
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发表时间：
2015-07-01
期刊：
影响因子：
4.2
通讯作者：
Cao, Jianping
中科院分区：
文献类型：
--
作者：
Nie, Jihua;Ge, Xin;Cao, Jianping
食管鳞状细胞癌（ESCC）是最常见的胃肠道肿瘤之一，死亡率高。microRNA（miRNAs）在肿瘤转移和进展中起重要的调控作用。miR-34 a已被证明通过多种靶基因与某些类型癌症的发展和转移相关，但其在ESCC中的功能和靶点尚不清楚。本研究的目的是通过RT-PCR和Western blot分析检测miR-34 a在食管鳞癌组织中的表达是否显著低于正常食管组织。结果显示，miR-34 a过表达可增加食管鳞癌细胞凋亡，减少克隆形成，但可通过抑制MMP-2和MMP-9的表达来抑制食管鳞癌细胞的侵袭和迁移。阴阳-1（Yin Yang-1，YY 1）是一种广泛分布的锌指蛋白GLI-Kruppel类转录因子，在食管鳞癌细胞系中被发现是miR-34 a的直接靶点。拯救实验表明，miR-34 a对侵袭和迁移的抑制作用是通过激活YY 1表达介导的。本研究结果表明，miR-34 a与ESCC迁移相关，并为ESCC提供了潜在的治疗和诊断靶点。
Esophageal squamous cell carcinoma (ESCC), one of the most common gastrointestinal tumors, is known for its high mortality rate. microRNAs (miRNAs) have been reported to play important regulatory roles in cancer metastasis and progression. miR-34a has been demonstrated to be associated with the development of and metastasis in certain types of cancer via various target genes, but its function and targets in ESCC are unknown. The aim of this study was to examine whether the expression of miR-34a was significantly decreased in ESCC tissues, compared with normal esophageal tissues using RT-PCR and western blot analysis. The results showed that miR-34a overexpression increased apoptosis and decreased clonogenic formation, but inhibited invasion and migration in ESCC cells by suppressing MMP-2 and -9 expression. Yin Yang-1 (YY1), a widely distributed transcription factor that belongs to the GLI-Kruppel class of zinc finger proteins, was found to be a direct target of miR-34a in ESCC cell lines. Rescue experiments indicated that the suppressive effect of miR-34a on invasion and migration was mediated by activating YY1 expression. Results of the present study showed that miR-34a is associated with ESCC migration and provides a potential therapeutic and diagnostic target for ESCC.